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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Major pathogenic steps in human lupus can be effectively suppressed by nucleosomal histone peptide epitope-induced regulatory immunity
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Major pathogenic steps in human lupus can be effectively suppressed by nucleosomal histone peptide epitope-induced regulatory immunity

机译：核小体组蛋白肽表位诱导的调节免疫可有效抑制人狼疮的主要致病步骤

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Abstract Low-dose tolerance therapy with nucleosomal histone peptide epitopes blocks lupus disease in mouse models, but effect in humans is unknown. Herein, we found that CD4~+CD25~highFoxP3~+ or CD4~+CD45RA~+FoxP3~lowT-cells, and CD8~+CD25~+FoxP3~+ T-cells were all induced durably in PBMCs from inactive lupus patients and healthy subjects by the histone peptide/s themselves, but in active lupus, dexamethasone or hydroxychloroquine unmasked Treg-induction by the peptides. The peptide-induced Treg depended on TGFbeta./ALK-5/pSmad 2/3 signaling, and they expressed TGF-beta precursor LAP. Lupus patients' sera did not inhibit Treg induction. The peptide epitope-induced T cells markedly suppressed type IIFN related gene expression in lupus PBMC. Finally, the peptide epitopes suppressed pathogenic autoantibody production by PBMC from active lupus patients to baseline levels by additional mechanisms besides Treg induction, and as potently as anti-IL6 antibody. Thus, low-dose histone peptide epitopes block pathogenic autoimmune response in human lupus by multiple mechanisms to restore a stable immunoregulatory state.
机译：摘要核小体组蛋白肽表位的低剂量耐受治疗可阻断小鼠模型中的狼疮病，但对人类的作用尚不清楚。在这里，我们发现非活动性狼疮患者的PBMCs中CD4〜+ CD25〜highFoxP3〜+或CD4〜+ CD45RA〜+ FoxP3〜lowT细胞和CD8〜+ CD25〜+ FoxP3〜+ T细胞均被持久诱导。健康受试者是由组蛋白肽本身引起的，但在活动性狼疮，地塞米松或羟氯喹中，未被肽掩盖的Treg诱导作用。肽诱导的Treg依赖于TGFbeta./ALK-5/pSmad 2/3信号传导，并且它们表达TGF-beta前体LAP。狼疮患者的血清没有抑制Treg的诱导。肽表位诱导的T细胞显着抑制了狼疮PBMC中IIFN型相关基因的表达。最后，除Treg诱导外，肽表位还通过其他机制将PBMC从活动性狼疮患者的致病性自身抗体产生抑制至基线水平，并且与抗IL6抗体一样有效。因此，低剂量组蛋白肽表位通过多种机制阻断人狼疮的致病性自身免疫反应，以恢复稳定的免疫调节状态。

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